Proteins are the workhorses of the cell, but nature sometimes has room for improvement. Now a team from the University of Washington's Institute for Protein Design (IPD) and the University of California San Francisco (UCSF) has created a new artificial protein that acts like a switch, turning regular cells into "smart cells."
In a pair of new studies, the IPD and UCSF team designed an artificial protein that can work inside living cells, manipulating the internal circuitry to perform specific actions. This it does by sensing changes in a cell's environment and releasing a key peptide that reacts in a specific way.
The team calls the design a Latching Orthogonal Cage/Key pRotein (LOCKR), and it's made up of several molecules that have different functions. There's a latch, a cage, a key and a bioactive peptide, and it's this structure that makes it particularly versatile.
When this biological switch is in the "off" position, the latch clamps the peptide to the cage, where it can't do anything but wait. When a molecule programmed to act like a key comes along, the latch suddenly flings open, releasing the peptide to the outside environment. This triggers a desired response on demand, whether that's the self-destruction of other proteins, the expression of a certain gene, or another cellular process.
The team demonstrated the technique with a version they call degronLOCKR. This system was designed to degrade a specific protein when it sensed something was wrong with the cell's regular activity. Reducing the levels of that targeted protein helps restore the cell's activity, meaning this "smart cell" can essentially correct these problems automatically as they occur.
"LOCKR, and more specifically, degronLOCKR, opens a whole new realm of possibility for programming cells to treat a wide range of debilitating conditions for which safe and effective treatments are not yet available," says Andrew Ng, co-first author of the two studies.
For the first practical use of this technology, the team is targeting traumatic brain injury (TBI). When these kinds of injuries occur, the body can sometimes overreact with inflammation levels that are too high. The team hopes that degronLOCKR can help sense inflammation and regulate it, to keep it to a safe but useful level.
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